In silico approach to design a multi-epitopic vaccine candidate targeting the non-mutational immunogenic regions in envelope protein and surface glycoprotein of SARS-CoV-2.

The novel corona virus (COVID-19) is a causative agent for severe acute respiratory syndrome (SARS-CoV-2) and responsible for the current human pandemic situation which has caused global social and economic commotion. The currently available vaccines use whole viruses whereas there is scope for peptide based vaccines. Thus, the global raise in statistics of this infection at an alarming rate evoked us to determine a novel and effective vaccine candidate against SARS-CoV-2. To find the potential vaccine candidate targets, immunoinformatics approaches were used to analyze the mutations in the envelope protein and surface glycoprotein and determine the conserved region; further specific T-cell epitopes VSLVKPSFY, SLVKPSFYV, RVKNLNSSR, SEETGTLIV, LVKPSFYVY, LTDEMIAQY, YLQPRTFLL, RLFRKSNLK, SPRRARSVA, AEIRASANL, TLLALHRSY, YSRVKNLNS and FELLHAPAT and B-cells epitopes TLAILTALRLCAYCCN and AGTITSGWTFGAGAAL were identified. The 3 D structure of epitope was predicted, refined and validated. The molecular docking analysis of multi-epitope vaccine candidates with TLR receptors, predicted effective binding. Overall, using bioinformatics approach this multi-epitopic target facilitates the proof of concept for SARS-CoV-2 conserved epitopic vaccine design.Communicated by Ramaswamy H. Sarma.

Internet of things-based energy-efficient optimized heuristic framework to monitor sportsperson's health.

BACKGROUND: Recently, wearable technologies have gained attention in diverse applications of the medical platform to guarantee the health and safety of the sportsperson with the assistance of the Internet of things (IoT) device. The IoT device's topology varies due to the shift in users' orientation and accessibility, making it impossible to assign resources, and routing strategies have been considered the prominent factor in the current medical research. Further, for sportspersons with sudden cardiac arrests, hospital survival rates are low in which wearable IoT devices play a significant role. OBJECTIVE: In this paper, the energy efficient optimized heuristic framework (EEOHF) has been proposed and implemented on a wearable device of the sportsperson's health monitoring system. METHOD: The monitoring system has been designed with cloud assistance to locate the nearest health centers during an emergency. The wearable sensor technologies have been used with an optimized energy-efficient algorithm that helps athletes monitor their health during physical workouts. The monitoring system has fitness tracking devices, in which health information is gathered, and workout logs are tracked using EEOHF. The proposed method is applied to evaluate and track the sportsperson's fitness based on case study analysis. RESULTS: The simulation results have been analyzed, and the proposed EEOHF achieves a high accuracy ratio of 97.8%, a performance ratio of 95.3%, and less energy consumption of 9.4%, delay of 13.1%, and an average runtime of 98.2% when compared to other existing methods.

Chronic musculoskeletal pain among elderly in rural Tamil Nadu: Mixed-method study.

OBJECTIVES: (1) To determine the prevalence of chronic pain of musculoskeletal origin at different body sites among elderly (≥60 years). (2) To study the determinants of chronic pain and the healthcare seeking behavior among elderly with chronic pain. (3) To explore the perceptions of chronic pain among elderly. MATERIALS AND METHODS: This study was done in 55 field practice villages of the Rural Health Training Centre (RHTC) of the Department of Community Medicine, SMVMCH, Puducherry. An Exploratory Mixed-Method study design, where a qualitative phase (in-depth interviews [IDI]) followed the quantitative phase (Survey). A representative sample of 850 respondents was selected by two-stage cluster sampling. A trained investigator did a house-to-house visit and interviewed selected elderly respondents by using predesigned and pretested questionnaire. The intensity of chronic pain was measured using the Functional Rating Scale and Numeric Rating Scale. The manual content analysis was done for qualitative data. Multiple logistic regression was performed on quantitative data. RESULTS: Qualitative data were described under two broad themes: (1) perceptions of elderly people about chronic pain and 2) healthcare seeking and coping mechanisms. Prevalence of chronic pain among the elderly respondents was found to be 47.6%. Most common site for chronic pain was knee joint (64.5%) followed by a low backache (21.7%). Most of the older people with chronic pain had mild-to-moderate and tolerable pain. Two predictors for chronic pain were the age of the respondent (adjusted OR -1.03, 95% CI = 1.01-1.05) and the presence of at least one chronic morbidity (adjusted OR -1.37, 95% CI = 1.03-1.82). CONCLUSIONS AND RECOMMENDATIONS: Since the chronic pain was found to be associated with aging and the presence of at least one of the chronic morbidities, it is crucial for treating community physicians to consider the comorbid conditions while managing chronic pain in elderly. Considering the complex nature of chronic pain in old age, the primary care physician should be trained in drug and context-specific nondrug interventions to address the biomedical causes and other cognitive-behavior factors, respectively, through active support from their family and neighborhood.

Fecal Fistula Communicating with a Femur Shaft Fracture Secondary to a Malpositioned Suprapubic Catheter: A Case Report.

BACKGROUND: Suprapubic catheter (SPC) insertion is a common urological procedure. Though considered a simple and safe procedure, complications are bound to occur if proper precautions are not taken during the procedure. The reported complications include gross hematuria, post-obstruction diuresis, insertion site skin-related complications, and intra-abdominal visceral injuries. Iatrogenic bowel injuries have been reported to occur as a complication in around 2.5% of cases. CASE REPORT: We report a very rare case of a bowel injury due to improper insertion of a SPC leading to fecal matter tracking along the muscle planes to reach the fracture site of the femur shaft and formation of an external fecal fistula along the lateral aspect of thigh, which according to us is the first reported case in the literature. CONCLUSIONS: This case report shows the devastating complication of a technically simple procedure done in an improper manner and successful management of a rare case of femur fracture with communicating fecal fistula. The purpose of this case report is to highlight the importance of taking proper precautions before the procedure.

Lower incidence of inappropriate shock therapy in patients with combined cardiac resynchronisation therapy defibrillators (CRT-D) compared with patients with non-CRT defibrillators (ICDs).

INTRODUCTION: A significant number of patients experience inappropriate shock therapy (IST) from implantable cardioverter-defibrillators (ICD). An increasing number of patients with advanced heart failure receive combined ICD and cardiac resynchronisation therapy devices (CRT-D). The incidence of IST in this group is less well described. We aimed to assess the incidence and predictors of IST in CRT-D patients. METHODS: A retrospective cohort study of prospectively collected data on patients who received an ICD and CRT-D between October 2007 and January 2009 at our institution were studied. The primary outcome measures were the IST event rate and all-cause mortality. RESULTS: A total of 185 patients with ICD/CRT-D (100/85) were included in the analysis. Eighteen patients experienced 35 episodes of IST during the follow-up (21 ± 13 months). There was a significantly lower IST cumulative event rate in the CRT-D vs. ICD group, 5% (CI: 1-13%) vs. 19% (95% CI: 11-30%) by 24 months, (p = 0.017). The majority of the IST was caused by atrial arrhythmias with atrial fibrillation accounting for 28 episodes of IST in nine patients. Multivariate analysis using Cox hazard model including baseline characteristics and coexisting appropriate shock therapy showed that a history of atrial fibrillation/flutter was the strongest independent predictor of IST with a hazard ratio of 3.53 (p = 0.019). CONCLUSION: Patients with CRT-D had a significantly lower incidence of IST compared with patients receiving an ICD. Given that atrial arrhythmia remained the commonest trigger for IST, our finding lends support to the hypothesis that CRT may reduce atrial fibrillation burden in patients receiving CRT-D.

Trends, indications and outcomes of cardiac implantable device system extraction: a single UK centre experience over the last decade.

BACKGROUND: The rising number of device implantation has seen a parallel in the rising numbers of lead extraction. Herein we have analysed our experience in cardiac device and lead extraction in a single tertiary centre over the last decade. METHOD: Retrospective analysis of all consecutive patients undergoing lead extractions performed between 2001 and 2010. Procedural success and complications as defined by the Heart Rhythm Society policy. RESULTS: A total of 745 leads were extracted with a procedural success of 98.9% [382 cases; partial success in 6.9% (26) cases] and failure in 1.1% (4). Major complication rate was 1% (four cases) and minor complication rate was 3.6%. By both univariate and multivariate analysis only duration of lead implantation was an indicator for success (p < 0.0001). The mean implantation time for failed lead extraction was 203 ± 64 months compared with 71.8 ± 16.5 months in the successful cohort (p < 0.0001). Laser-assisted extraction was required in 176 cases. With regard to extraction indication, lead malfunction/recall showed a significant increase during the study period (p = 0.03). On time trend analysis the rise in coronary sinus (CS) lead extraction over time was significant. (p = 0.02) Despite a trend for increased laser use over time this did not achieve statistical significance, p = 0.06. CONCLUSIONS: A decade's experience of percutaneous lead extraction suggests that a high procedural success rate with a low complication rate is achieved in a high-volume centre. During this time, an increase in both defibrillator and CS lead explantation and a rising trend in laser assistance with almost 50% of cases needing laser usage were observed.

Inadvertent identification of the left pericardiophrenic vein following laser lead extraction to guide left ventricular lead placement.

Phrenic nerve stimulation (PNS) is a frequent occurrence in patients implanted with a cardiac resynchronization therapy device. We present a case where identification of the left pericardiophrenic vein, which runs alongside the phrenic nerve, was used to guide left ventricular lead placement in order to minimize the risk of PNS.

Male gender and chronic obstructive pulmonary disease predict a poor clinical response in patients undergoing cardiac resynchronisation therapy.

AIMS: Current guidelines advocate cardiac resynchronisation therapy (CRT) in patients with class III/IV New York Heart Association (NYHA) heart failure, depressed left ventricular function and a broad QRS. However, a significant proportion of patients do not derive any benefit from CRT. The aim of this study was to identify clinical, electrocardiographic and echocardiographic predictors of response to CRT. METHODS: A retrospective analysis of patients undergoing CRT in our institution was performed. A favourable clinical response to CRT was defined as an improvement in NYHA Heart failure class of ≥ 1 and lack of hospitalisation with heart failure. Comparisons were made between responders and non-responders in terms of baseline characteristics and potential predictors of CRT response (QRS width, presence of left bundle branch block, atrial fibrillation, evidence of mechanical dyssynchrony on echocardiography and LV lead position). RESULTS: A total of 164 patients had full follow-up data. The mean follow-up was 293 days. Of patients undergoing CRT, 90 (58.9%) had a favourable clinical response to CRT. Predictors of a lack of clinical response to CRT were male gender (p = 0.012) and chronic obstructive pulmonary disease (COPD) (0.008). Pre-implant echocardiographic dyssynchrony assessment appeared not to predict response to CRT (p = 0.87); however, there was a trend towards a positive response in those patients with significant dyssynchrony (p = 0.09) defined as interventricular delay > 40 ms or maximal LV delay of > 80 ms. CONCLUSION: Male gender and coexisting COPD were shown to be independent predictors of non-response to CRT in this cohort of patients fulfilling current criteria for CRT.

Characterization of a new antifungal lipid transfer protein from wheat.

Lipid transfer proteins (LTPs) are members of the family of pathogenesis-related proteins (PR-14) that are believed to be involved in plant defense responses. In this study, a novel gene Ltp 3F1 encoding an antifungal protein from wheat (Sumai 3) was subcloned, overexpressed in Escherichia coli BL-21 (DE3) and enriched using ammonium sulfate fractionation followed by gel permeation chromatography. Molecular phylogeny analyses of wheat Ltp 3F1 gene showed a strong identity to other plant LTPs. Predicted three-dimensional structural model showed the presence of 6 alpha-helices and 9 loop turns. The active site catalytic residues Gly30, Pro50, Ala52 and Cys55 may be suggested for catalyzing the reaction involved in lipid binding. SDS-PAGE analysis confirmed the production of recombinant fusion protein. The LTP fusion protein exhibited a broad-spectrum antifungal activity against Alternaria sp., Rhizoctonia solani, Curvularia lunata, Bipolaris oryzae, Cylindrocladium scoparium, Botrytis cinerea and Sarocladium oryzae. Gene cassette with cyanamide hydratase (cah) marker and Ltp 3F1 gene was constructed for genetic transformation in tobacco. Efficient regeneration was achieved in selective media amended with cyanamide. Transgenic plants with normal phenotype were obtained. Results of PCR and Southern, Northern and Western hybridization analyses confirmed the integration and expression of genes in transgenic plants. Experiments with detached leaves from transgenic tobacco expressing Ltp 3F1 gene showed fungal resistance. Due to the innate potential of broad-spectrum antifungal activity, wheat Ltp 3F1 gene can be used to enhance resistance against fungi in crop plants.

Heterologous expression of new antifungal chitinase from wheat.

Chitinases (EC 3.2.1.14) have been grouped into seven classes (class I-VII) on the basis of their structural properties. Chitinases expressed during plant-microbe interaction are involved in defense responses of host plant against pathogens. In the present investigation, chitinase gene from wheat has been subcloned and overexpressed in Escherichia coli BL-21 (DE3). Molecular phylogeny analyses of wheat chitinase indicated that it belongs to an acidic form of class VII chitinase (glycosyl hydrolase family 19) and shows 77% identity with other wheat chitinase of class IV and low level identity to other plant chitinases. The three-dimensional structural model of wheat chitinase showed the presence of 10 alpha-helices, 3 beta-strands, 21 loop turns and the presence of 6 cysteine residues that are responsible for the formation of 3 disulphide bridges. The active site residues (Glu94 and Glu103) may be suggested for its antifungal activity. Expression of chitinase (33 kDa) was confirmed by SDS-PAGE and Western hybridization analyses. The yield of purified chitinase was 20 mg/L with chitinase activity of 1.9 U/mg. Purified chitinase exerted a broad-spectrum antifungal activity against Colletotrichum falcatum (red rot of sugarcane) Pestalotia theae (leaf spot of tea), Rhizoctonia solani (sheath blight of rice), Sarocladium oryzae (sheath rot of rice) Alternaria sp. (grain discoloration of rice) and Fusarium sp. (scab of rye). Due to its innate antifungal potential wheat chitinase can be used to enhance fungal-resistance in crop plants.

Cloning and overexpression of antifungal barley chitinase gene in Escherichia coli.

Plant chitinases are pathogenesis-related proteins, which are believed to be involved in plant defense responses to pathogen infection. In this study, chitinase gene from barley was cloned and overexpressed in Escherichia coli. Chitinase (35 kDa) was isolated and purified. Since the protein was produced as insoluble inclusion bodies, the protein was solubilized and refolded. Purified chitinase exerted broad-spectrum antifungal activity against Botrytis cinerea (blight of tobacco), Pestalotia theae (leaf spot of tea), Bipolaris oryzae (brown spot of rice), Alternaria sp. (grain discoloration of rice), Curvularia lunata (leaf spot of clover) and Rhizoctonia solani (sheath blight of rice). Due to the potential of broad-spectrum antifungal activity barley chitinase gene can be used to enhance fungal-resistance in crop plants such as rice, tobacco, tea and clover.

Can iron status be improved in each of the three trimesters? A community-based study.

OBJECTIVE: Intervention with iron supplementation, deworming, and information, education and communication (IEC) to improve the haematological status among each of the three trimesters of pregnant women in a rural community. DESIGN: A community-based study was carried out using a two-group pre-post experimental design in a rural community. SETTING: Two rural blocks in Vellore district were selected for the study. KV Kuppam block with a population of 120,000 and the adjacent Gudiyatham block with a population of 132,000 served as study and control areas for the study. SUBJECTS: Using a multistage sampling, initially 50% of the panchayats, the local village administrative units, were randomly selected and all pregnant women were the subjects. In the pre-intervention survey 458 and 387 pregnant women had haemoglobin tested and the post-intervention survey covered 403 and 425 pregnant women in the study and control areas, respectively. Similarly serum ferritin was tested in a randomly selected sub-sample with 254 and 191 pregnant women before intervention and in 216 and 223 pregnant women after intervention in both study and control areas, respectively. INTERVENTION: Iron supplementation and deworming were provided to all pregnant women in the study area from the fourth month of their pregnancy. An intensive information, education and communication was carried out with facts on anaemia and diet modification to each pregnant woman, using a one-to-one approach in the community, and a group method in the mobile clinics. This was carried out for a period of 18 months. RESULTS: A significant decrease in the prevalence of anaemia was found, from 56.1% to 25.07% (P<0.001), 73. 4% to 49.2% (P<0.001) and 68.8% to 56.8% (P<0.01) among women in the first, second and third trimesters, respectively, in the intervention area. Significant (P<0.001) increases in the mean haemoglobin of 0.85 g/dl (95% CI 10.18-10.84, 11.09-11.63), 0.59 g/dl (95% CI 9.98-10.34, 10.55-10.95) and 0.36 g/dl (95% CI 9.93-10. 33, 10.25-10.73) were also observed in each of the groups. CONCLUSION: A comprehensive community-based intervention with iron supplementation, helminthic treatment and increase in knowledge using IEC through effective strategies can improve the haematological status of pregnant women in each trimester.